IntroductionIn the past, canine osteoarthritis (OA), also known as degenerative joint disease (DJD), was predominantly thought to be an age-related condition caused by wear and tear on the joints over time. Consequently, management of OA focused on reducing clinical signs and relieving pain in aging dogs. With this approach, OA can go untreated until the disease has advanced and a dog shows obvious changes in activity or clear signs of pain.

Although older age is one of many OA risk factors, osteoarthritis is not inevitable as a dog ages. In fact, there is no scientific evidence that age and exercise cause OA in dogs.1 As one study notes,

...a lifetime of regular weight bearing exercise in dogs with normal joints did not cause alterations in the structure and mechanical properties of articular cartilage that might lead to joint degeneration.1

OA is a progressive disease with no known cure that can lead to chronic inflammation, irreversible joint damage, escalating pain and immobility. That’s why there’s a growing awareness of the need to rethink OA and turn the focus to early diagnosis and treatment. “Early intervention has the greatest potential for providing the most effective management of OA since it provides an opportunity to initiate an appropriate long-term care plan and disrupt the progressive, vicious cycle...”2

What’s needed is a proven treatment that not only alleviates the signs of OA but also reduces and slows its progression. That describes Adequan® Canine (polysulfated glycosaminoglyan). After 20 years, it’s still the only FDA-approved Disease-Modifying OsteoArthritis Drug (DMOAD) for dogs with OA.

The purpose of this technical bulletin is to explain the unique characteristics of Adequan Canine and the distinct advantages it can provide veterinarians as they manage OA in dogs.

K E Y P O I N T S

Introduction

The impact of a DMOAD

Mode of action

Proven efficacy

Safety

Highlight: COAST Canine OsteoArthritis Staging Tool

Clinical implications for proactive management

Conclusion

Adequan® Canine (polysulfated glycosaminoglycan)

A Disease-Modifying Osteoarthritis DrugT E C H N I C A L B U L L E T I N

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The impact of a DMOAD From chasing a ball to simply walking up stairs, mobility is vital to a healthy quality of life for dogs. That’s why canine osteoarthritis or degenerative joint disease is so devastating. Although OA is the most common cause of chronic pain in dogs,3 it isn’t just an “old dog” problem, as a myriad of studies have confirmed. Breed, obesity, repetitive stress, injuries, infections, poor nutrition and genetics are known risk factors, and OA clearly affects dogs of all ages.

Active dogs need healthy cartilage to maintain effective joint function. In joints with osteoarthritis, the complex process of cartilage repair is unable to keep up with damage. Key components in the cartilage and synovial fluid are lost and not replaced. Over time, this can lead to bone-on-bone contact, chronic inflammation, swelling and escalating pain.

Currently, there is no known cure for OA, and its management has tended to focus on mitigating clinical signs (such as pain and inflammation) with symptom-modifying drugs or nutritional supplements. Although symptom-modifying treatments may alleviate signs of OA, they do not affect or help slow the progression of the disease.

As it progresses, OA can lead to exposed bone and cartilage damage.

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A disease-modifying osteoarthritis drug works differently. By definition, a DMOAD is capable of slowing and stabilizing the progression of osteoarthritis along with the damage it causes to joints. And there is one DMOAD approved for use by veterinarians:

Adequan® Canine (polysulfated glycosaminoglyan) is the only FDA-approved disease-modifying osteoarthritis drug (DMOAD) that inhibits cartilage loss in a dog’s synovial joints. It’s also the only pharmaceutical available that empowers veterinarians to proactively treat the disease and not just the signs of OA.5

The Impact of a DMOAD

EXPOSED BONE

DAMAGED CARTILAGE

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Mode of actionAdequan® Canine (polysulfated glycosaminoglycan) is a prescription drug to help reduce the loss of articular cartilage, slow the progression of joint structural damage, and promote healthy joint component maintenance. The specific mechanism of Adequan® in canine joints is unknown.5 However, much is known from multiple studies, which helps to explain its proven effects for dogs with OA.

Based on its approved indications for use, Adequan Canine is recommended for intramuscular injection for the control of signs associated with non-infectious degenerative and/or traumatic arthritis of canine synovial joints.4

Once Adequan Canine is injected, it enters the bloodstream, crosses the synovial membrane into the synovial fluid, and enters the articular cartilage by diffusion. It begins to reach joint synovial fluid within two hours and detectable levels are maintained in the synovial fluid and articular cartilage for up to three days (72 hours).4

Adequan® Canine enters the synovial membrane through the bloodstream.

Mode of Action

T E C H N I C A L B U L L E T I N

Adequan® Canine brand of polysulfated glycosaminoglycan (PSGAG)

INDICATIONS Adequan® Canine is recommended for intramuscular injection for the control of signs associated with non-infec-tious degenerative and/or traumatic arthritis of canine synovial joints.

IMPORTANT SAFETY INFORMATION Adequan® Canine should not be used in dogs who are hypersensitive to PSGAG or who have a known or suspected bleeding disorder. It should be used with caution in dogs with renal or hepatic impairment. Adverse reactions in clinical studies (transient pain at injection site, transient diarrhea, and abnormal bleeding) were mild and self-limiting. In post approval experience, death has been reported in some cases; vomiting, anorexia, depression/lethargy and diarrhea have also been reported. The safe use of PSGAG in breeding, pregnant or lactating dogs has not been evaluated. Caution: Federal law restricts this drug to use by or on the order of a licensed veterinarian.

For additional safety information, please see Full Prescribing Information at adequancanine.com.

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Proven efficacyEfficacy studies have shown Adequan® Canine (polysulfated glycosaminoglycan) inhibits the loss of key joint components, including:5

• Proteoglycan, a macromolecule that helps to form connective tissue.

• Collagen, a structural protein that’s one of the major building blocks of bones, tendons and ligaments.

• Hyaluronic acid, an important lubricating molecule that helps to restore joint lubrication.

In vitro laboratory studies have confirmed that Adequan Canine inhibits catabolic enzymes that destroy these key molecules.

At the same time, Adequan Canine has been shown to enhance the activity of anabolic enzymes that help provide the valuable building blocks for cartilage repair in joints. This combination ultimately helps to renew damaged cartilage.

In a controlled field trial to determine efficacy and safety,4 the Adequan Canine treated group showed a trend toward greater improvement versus the placebo group for all seven key parameters:

• Lameness at a walk• Gait analysis at a trot• Pain on manipulation of limb• Range of motion• Functional disability• Radiographic scoring• Clinician’s subjective response

Dogs (n = 51) with radiographically detectable degenerative joint disease in one or two limbs were administered intramuscular injections twice weekly for 4 weeks (total of 8 injections). Dogs treated with Adequan Canine had statistically significant improvement in range of motion and orthopedic scores compared with placebo-treated control dogs.4

Adequan® Canine inhibits the damaging enzymatic activity and loss of key joint components.

Adequan® Canine helps enhance enzymatic activity to promote a matrix rich in key components.

Proven Efficacy

T E C H N I C A L B U L L E T I N

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“ “ SafetyDose selection for Adequan® Canine (polysulfated glycosaminoglycan) was based on published studies concerning the use of polysulfated glycosaminoglycan in osteoarthritis models in dogs. The selected dose of 2 mg/lb was shown to have an adequate margin of safety in dogs, and was confirmed in a clinical field trial. These results demonstrated that Adequan Canine, when used according to the conditions set forth in the labeling, is safe and effective.4

As noted on its label, studies to establish the safety of Adequan Canine in breeding, pregnant or lactating dogs have not been conducted.4 Use with caution in dogs with renal or hepatic impairment.

Clinical implications for proactive managementAs the most common chronic pain condition recognized in dogs,3 osteoarthritis has garnered the attention of researchers, veterinary experts and orthopedic specialists for decades. More attention has brought an even greater understanding about the need to think earlier and younger to be proactive in diagnosing and treating OA because once cartilage wears away completely, it can’t be restored. In order to help dogs stay as active as possible, for as long as possible, it’s vital to preserve articular cartilage. This may explain why more experts now agree on the need to focus on early diagnosis and treatment of OA.

Early intervention has the greatest potential for providing the most effective management of OA since it provides an opportunity to initiate an appropriate long-term care plan and disrupt the progressive, vicious cycle of multidimensional deterioration.2

The day-to-day reality for dogs with OA is painful, and this has also lead to a plethora of symptom-modifying options, such as NSAIDs, nutraceuticals and supplements predominantly focused on alleviating pain and observable clinical symptoms. While these products in a multi-modal approach can provide temporary relief, they don’t address the underlying cause or slow the progression of OA.

Adequan Canine is completely different, with its classification as a disease-modifying osteoarthritis drug (DMOAD) and the positive results it delivers for dogs with OA.5

For more than 20 years, it has demonstrated the unique ability to help:5

• restore joint lubrication• relieve inflammation• renew the building blocks of healthy cartilage

In essence, as an integral part of the multi-modal approach, Adequan Canine is proven to help slow the progression of the disease.

T E C H N I C A L B U L L E T I N

Safety and Clinical Implications

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“ “ COAST was developed by a group of international small animal orthopedic, anesthesia and pain management specialists inspired by “…a desire to improve the situation for dogs with OA…and to help veterinarians with the proactive, stage-specific diagnosis and monitoring of OA in dogs.”2

It’s an effective tool designed to help primary care veterinarians and their clients work together to:

• Assess dogs with OA risk factors.• Identify clinical signs of OA.• Provide an objective baseline and follow-up metrics

to evaluate the success of therapy.

Osteoarthritis (OA) is the most common chronic pain condition recognized in dogs.1 However, evaluating OA in our pets is not easy. Dogs instinctively try to hide their signs of discomfort, and those signs may be subtle or brief in duration (a few seconds or minutes) based on the stage or progression of the underlying problem. A dog may act uncomfortable at home but not indicate this at the veterinary clinic. That’s why it’s a good idea for you (a responsible dog owner) to learn to recognize certain telling behaviors in your dog.

This questionnaire will help you to identify your dog’s current level of pain and discomfort while also helping guide the discussion with your veterinarian for your dog’s OA evaluation. The success of any treatment, if and when needed, and the strategy for ongoing care is a collaborative effort between you and your veterinarian.

Signs of Discomfort:While this list is not comprehensive, here are a few indications your dog may be experiencing discomfort or pain:

1. M Epstein DVM, DABVP, CVPP; Prevention and Management of Pain in Canine Patients, Canine Sports Medicine and Rehabilitation, Sec. Ed., Chapter 19, Pg. 493; 2018.

} Change in breathing pattern (i.e. excessive panting)

} Excessive licking or grooming

} Restlessness or inability to get comfortable

} Agitation or aggression

} Limping or abnormal gait or change in gait

} Change in appetite

} Change in sleeping habits

} Vocalization (cries, whimpers, groans, etc.)

} Hiding or seeking attention

Assessing Discomfort in Your Dog Questionnaire for dog owners.

Complete the questionnaire on the reverse side and share with your veterinarian.

Canine OsteoArthritis Staging ToolThis COAST helps you and your clients identify the signs of OA while providing an objective baseline and subsequent success metrics for initiated therapy.

Patient Name:_________________________

Owner Name:_________________________

Date: __________________________________

0 1 2 3

Static Posture

Normal

Breed-appropriate with proper limb loading and

normal body weight distribution between

forelimbs and hindlimbs.

Mildly Abnormal

Subtle abnormality in limb loading and light shift in body weight distribution.

Moderately Abnormal

Obvious abnormality in limb loading and obvious shift in

body weight distribution.

Severely Abnormal

Stands with difficulty and unease. Severe shift in

body weight distribution.

Motion

Normal

Fluent and symmetric gait with appropriate

weight bearing and body weight distribution.

Mildly Abnormal

Subtle lameness, asymmetry and gait

stiffness. Possible impact with some activities, yet no

difficulty getting up.

Moderately Abnormal

Consistent gait abnormalities and some

difficulty getting up, obvious stiffness, change in body weight, and reduction

in use of affected limb.

Severely Abnormal

Severe weight shift and lameness. Has difficulty

getting up and struggles.

Grade the Dog

EVA

LUA

TIO

N B

Y V

ETER

INA

RIA

N

Grade the Joint

EV

ALU

ATIO

N B

Y V

ETE

RIN

AR

IAN

Input the dog’s results in the chart below.

GRADE THE DOG GRADE THE JOINT OVERALL SEVERITY

LEVELOWNER

QUESTIONNAIREPOSTURE MOTION

PAIN UPON MANIPULATION

PHYSICAL EXAMINATION

RADIOGRAPHS

Level (highest number)

Next, plot the Overall Severity Level in the chart at the bottom on the reverse page. This will determine the dog’s Stage of OA.

LEVEL of POSTURE

LEVEL of MOTION

0 1 2 3

Pain Upon Manipulation

None Mild Moderate Severe

Passive Range of Movement

Normal

Mildly Abnormal

Slight joint thickening with minimal ROM

reduction and no crepitus.

Moderately Abnormal

Obvious joint thickening with obvious ROM

reduction and muscle atrophy.

Severely Abnormal

Extremely limited ROM with severe muscle

atrophy, joint thickening and crepitus. Anatomical misalignment and loss of normality on palpation.

Radiography

No Signs of OA

If preclinical “at risk,” the dog may have

evidence of risk factors such as dysplasia

and/or trauma, excess weight, age.

Mild Signs of OA

Early signs of OA and minimal osteophytes.

Moderate Signs of OA

Obvious osteophytes.

Severe Signs of OA

Advanced osteophytes and remodeling.

LEVEL of PAIN

LEVEL of ROM

LEVEL from RADIOGRAPH

© 2020, American Regent, Inc. PP-AC-US-0248 04/2020

C O A S T :

C A N I N E O S T E O A R T H R I T I S S T A G I N G T O O L

COAST consists of two key steps, which are repeated at monitoring intervals tailored to the requirements of the individual dog:2

Grading to evaluate the affected joint(s) and establish the impact of OA on the dog as a whole.

Defining the stage of OA to help guide treatment and monitor the disease as it progresses.

Pet owner information is obtained as they complete a questionnaire, which lets them record their observations about the overall degree of their dog’s discomfort and pain level when performing basic daily activities.

COAST is a useful tool which can help veterinarians and pet owners more readily identify dogs at risk and diagnose OA early based on standardized criteria.

Ultimately, an effective staging tool like this may help improve pain control and general clinical management of dogs with OA by providing standardized ‘scores’ over time than can be related to treatment efforts.2

COAST forms and the pet owner questionnaire are available for veterinary practices from American Regent Animal Health. To learn more visit adequancanine.com/Resource-Library.

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Conclusion

T E C H N I C A L B U L L E T I N

References1. Newton PM, Mow VC, Gardner TR, et al.

Winner of the 1996 Cabaud Award. The effect of lifelong exercise on canine articular cartilage. Am J Sports Med 1997; 25:282-287. [DML]

2. Face validity of a proposed tool for staging canine osteoarthritis: Canine OsteoArthritis Staging Tool (COAST), T. Cachon, O. Frykman, J.F. Innes, B.D.X. Lascelles, M. Okumura, P. Sousa, F. Staffieri, P.V. Steagall, B. Van Ryssen, COAST Development Group, The Veterinary Journal, 235 (2018) 1-8.

3. 2016 NAVC Proceedings, Osteoarthritis in Dogs and Cats: Novel Therapeutic Advances, M Epstein, DVM, DABVP C/F, CVPP; K Kirkby Shaw, DVM, MS, PhD, DACVS, DACVSMR.

4. Adequan® Canine (polysulfated glycosaminoglycan) NADA 141-038 FOI Summary, 1997.

5. Adequan Canine Package Insert, Rev. 1/19.

6. E. Mele, Epidemiology of Osteoarthritis. Veterinary Focus 17, 4–10 (2007).

7. “Osteoarthritis: Structural Endpoints for the Development of Drugs, Devices, and Biological Products for Treatment Guidance for Industry,” U.S. Department of Health and Human Services, Food and Drug Administration. August 2018.

ConclusionMany supplements and over-the-counter products may make similar claims to Adequan® Canine (polysulfated glycosaminoglycan). However, these products do not have the structured and qualified product testing and trials Adequan Canine completed to become the only FDA-approved DMOAD. In comparison, Adequan Canine is a DMOAD clinically proven to help modify the disease. As an FDA-approved pharmaceutical, it is required to be prescribed by a licensed veterinarian, which offers the added assurance of the most accurate dosing, safe use, and appropriate monitoring.

It’s equally important to recognize the advantages of proactively identifying dogs at risk for early diagnosis and treatment. Years of research and clinical experience have confirmed osteoarthritis is not just an age-related disease. Many risk factors can contribute to the progression of canine OA, including breed, obesity, infections and genetics. In fact, more than half of canine arthritis cases diagnosed are in dogs between 8-13 years of age.6

Although canine osteoarthritis continues to be an ongoing challenge for veterinarians, early intervention can be the most effective way to help manage this disease.2 A proactive approach is supported by FDA guidance, which emphasizes the need for diagnosis and treatments to inhibit the structural damage or target the underlying pathophysiology of OA to reduce pain and help slow the complications of joint damage, deterioration and failure.7

Adequan Canine can help to meet that need because it’s proven to help:

• Decrease inflammation of the synovial membrane, which is associated with the onset of osteoarthritis.

• Increase hyaluronic acid in the synovial fluid, which is needed to keep joints lubricated.

With growing awareness of the importance to think earlier and younger to proactively diagnose and treat canine OA, Adequan Canine can make a genuine impact for veterinarians and their canine OA patients. It is proven to help slow the progression of the disease, help reduce damage, and promote improved joint health and mobility. It really is, The difference between feeling better and getting better.®

NOTE: To learn more about the FDA requirements for approval as a disease-modifying osteoarthritis drug (DMOAD), download a copy of “Technical Bulletin: What is a DMOAD?” at https://rethinkoa.com/what-is-a-dmoad/

7Discover if Adequan® Canine is the right choice for your patients.

Caution: Federal law restricts this drug to use by or on the order of a licensed veterinarian.Description: The active ingredient in Adequan® Canine is polysulfated glycosaminoglycan(PSGAG). Polysulfated glycosaminoglycan is a semi-synthetic glycosaminoglycan prepared byextracting glycosaminoglycans (GAGs) from bovine tracheal cartilage. GAGs are polysaccharidescomposed of repeating disaccharide units. The GAG present in PSGAG is principally chondroitinsulfate containing 3 to 4 sulfate esters per disaccharide unit. The molecular weight for PSGAGused in the manufacture of Adequan® is 3,000 to 15,000 daltons.Each mL of Adequan® Canine contains 100 mg of PSGAG, 0.9% v/v benzyl alcohol as apreservative, and water for injection q.s. to 1 mL. Sodium hydroxide and/or hydrochloric acidadded when necessary to adjust pH. The solution is clear, colorless to slightly yellow.Pharmacology: The specific mechanism of action of Adequan® in canine joints is not known.PSGAG is characterized as a “disease modifying osteoarthritis drug”. Experiments conducted in vitro have shown PSGAG to inhibit certain catabolic enzymes which have increased activity ininflamed joints, and to enhance the activity of some anabolic enzymes. For example, PSGAG hasbeen shown to significantly inhibit serine proteinases. Serine proteinases have beendemonstrated to play a role in the Interleukin-l mediated degradation of cartilage proteoglycansand collagen. PSGAG is reported to be an inhibitor of Prostaglandin E2 (PGE2) synthesis. PGE2has been shown to increase the loss of proteoglycan from cartilage. PSGAG has been reported toinhibit some catabolic enzymes such as elastase, stromelysin, metalloproteases, cathepsin B1,and hyaluronidases, which degrade collagen, proteoglycans, and hyaluronic acid in degenerativejoint disease. Anabolic effects studied include ability to stimulate the synthesis of protein, collagen,proteoglycans, and hyaluronic acid in various cells and tissues in vitro. Cultured human and rabbitchondrocytes have shown increased synthesis of proteoglycan and hyaluronic acid in thepresence of PSGAG. PSGAGs have shown a specific potentiating effect on hyaluronic acidsynthesis by synovial membrane cells in vitro. Absorption, distribution, metabolism, and excretion of PSGAG following intramuscular injectionhave been studied in several species, including rats, rabbits, humans, horses and dogs.Studies in rabbits showed maximum blood concentrations of PSGAG following IM injection werereached between 20 to 40 minutes following injection, and that the drug was distributed to alltissues studied, including articular cartilage, synovial fluid, adrenals, thyroid, peritoneal fluid,lungs, eyes, spinal cord, kidneys, brain, liver, spleen, bone marrow, skin, and heart.Following intramuscular injection of PSGAG in humans, the drug was found to be bound to serumproteins. PSGAG binds to both albumin and chi- and beta-globulins and the extent of the bindingis suggested to be 30 to 40%. Therefore, the drug may be present in both bound and free form inthe bloodstream. Because of its relatively low molecular weight, the synovial membrane is not asignificant barrier to distribution of PSGAG from the bloodstream to the synovial fluid. Distributionfrom the synovial fluid to the cartilage takes place by diffusion. In the articular cartilage the drug isdeposited into the cartilage matrix. Serum and synovial fluid distribution curves of PSGAG have been studied in dogs and appearsimilar to those found in humans and rabbits.In rabbits, metabolism of PSGAG is reported to take place in the liver, spleen, and bone marrow.Metabolism may also occur in the kidneys. PSGAG administered intramuscularly and not proteinbound or bound to other tissues is excreted primarily via the kidneys, with a small proportionexcreted in the feces. Toxicity: In a subacute toxicity study, 32 adult beagle dogs (4 males and 4 females per treatmentgroup) received either 0.9% saline solution or PSGAG at a dose of 5 mg, 15 mg, or 50 mg per kgof body weight (approximately 2.3, 6.8, or 22.7 mg/lb), via intramuscular injection twice weekly for13 weeks. PSGAG doses represent approximately 1X, 3X, and 10X the recommended dosage of2 mg/lb, and more than 3 times the recommended 4-week duration of treatment. Necropsies wereperformed 24 hours after the final treatment. During week 12, one dog in the 50 mg/kg dosagegroup developed a large hematoma at the injection site which necessitated euthanasia. No othermortalities occurred during the treatment period. Statistically significant changes in the 50 mg/kggroup included increased prothrombin time, reduced platelet count, an increase in ALT andcholesterol, and increased liver and kidney weights. Increased cholesterol and kidney weightswere also noted in the 15 mg/kg group. Microscopic lesions were noted in the liver (Kupffer cellscontaining eosinophilic foamy cytoplasm), kidneys (swollen, foamy cells in the proximalconvoluted tubules), and lymph nodes (macrophages with eosinophilic foamy cytoplasm) in the15 mg/kg and 50 mg/kg groups. Intramuscular inflammation, hemorrhage, and degeneration wereseen in all 3 PSGAG treated groups; the incidence and severity appeared dose related.Efficacy: Efficacy of Adequan® Canine was demonstrated in two studies. A laboratory study usingradiolabeled PSGAG established distribution of PSGAG into canine serum and synovial fluidfollowing a single intramuscular injection of 2 mg/lb. A clinical field trial was conducted in dogsdiagnosed with radiographically-confirmed traumatic and/or degenerative joint disease of 1 or 2 joints. Joints evaluated included hips, stifles, shoulders, hocks and elbows. Fifty-one dogs wererandomly assigned to receive either Adequan® Canine at 2 mg/lb of body weight or 0.9% saline.

Brand of Polysulfated GlycosaminoglycanSolution 100 mg/mL in a 5 mL preserved

Multiple dose vial for intramuscular use in dogs.

®

Both treatments were administered by intramuscular injection twice weekly for 4 weeks (8 injections total). Investigators administering treatment and evaluating the dogs were unaware ofthe treatment assignment. A total of 71 limbs in 51 dogs were evaluated. Of these, 35 limbs in 24 dogs were in the Adequan® Canine treated group. Each lame limb was scored for lameness ata walk, lameness at a trot, pain, range of motion, and functional disability. The scores for theindividual parameters were combined to determine a total orthopedic score. At the end of thetreatment period, dogs treated with Adequan® Canine showed a statistically significantimprovement in range of motion and total orthopedic score over placebo treated control dogs.Indications and Usage: Adequan® Canine is recommended for intramuscular injection for thecontrol of signs associated with non-infectious degenerative and/or traumatic arthritis of caninesynovial joints.Contraindications: Do not use in dogs showing hypersensitivity to PSGAG. PSGAG is asynthetic heparinoid; do not use in dogs with known or suspected bleeding disorders.Precautions: The safe use of Adequan® Canine used in breeding, pregnant, or lactating dogshas not been evaluated. Use with caution in dogs with renal or hepatic impairment.Adverse Reactions: In the clinical efficacy trial, 24 dogs were treated with Adequan® Caninetwice weekly for 4 weeks. Possible adverse reactions were reported after 2.1% of the injections.These included transient pain at the injection site (1 incident), transient diarrhea (1 incident eachin 2 dogs), and abnormal bleeding (1 incident). These effects were mild and self-limiting and didnot require interruption of therapy.Post Approval Experience (2014)The following adverse events are based on voluntary, post-approval reporting. Not all adversereactions are reported to FDA/CVM. It is not always possible to reliably estimate the adverseevent frequency or establish a causal relationship to product exposure using these data. Thesigns reported are listed in decreasing order of reporting frequency.Vomiting, anorexia, depression/lethargy, diarrhea.In some cases, death has been reported.To report suspected adverse drug events, contact American Regent, Inc. at 1- 800- 458- 0163. Foradditional information about adverse drug experience reporting for animal drugs, contact FDA at1-888-FDA-VETS or http://www.fda.gov/AnimalVeterinary/SafetyHealth.Warnings: Not for use in humans. Keep this and all medications out of reach of children.DOSAGE AND ADMINISTRATION: Practice aseptic techniques in withdrawing each dose todecrease the possibility of post-injection bacterial infections. Adequately clean anddisinfect the stopper prior to entry with a sterile needle and syringe. Use only sterileneedles, and use each needle only once.The vial stopper may be punctured a maximum of 10 times.The recommended dose of Adequan® Canine is 2 mg/lb body weight (.02 mL/lb, or 1 mL per50 lb), by intramuscular injection only, twice weekly for up to 4 weeks (maximum of 8 injections).Do not exceed the recommended dose or therapeutic regimen. Do not mix Adequan® Canine withother drugs or solvents.Storage Conditions: Store at 20° to 25°C (68° to 77°F) excursions permitted to 15° to 30°C (59° to 86°F) (See USP Controlled Room Temperature). Avoid prolonged exposure totemperatures 40°C (104°F).Use within 28 days of first puncture and puncture a maximum of 10 times. Dispose of spentneedles in accordance with all federal, state and local environmental laws.How Supplied: Adequan® Canine Solution 100 mg/mL in a 5 mL preserved multiple dose vial.NDC 10797-975-02 5 mL Multiple Dose Vials Packaged 2 vials per boxAMERICAN REGENT, INC.ANIMAL HEALTHShirley, NY 11967(631) 924-4000(800) 458-0163

NADA 141-038, Approved by FDAMade in U.S.A. Rev. 1/19

Brand of Polysulfated GlycosaminoglycanSolution 100 mg/mL in a 5 mL preserved

Multiple dose vial for intramuscular use in dogs.

®

IN975MG #44454

For more information:

800-458-0163 adequancanine.com

All trademarks are the property of American Regent, Inc.© 2020, American Regent, Inc. PP-AC-US-0247 04/2020